Evaluation of intervertebral disc degeneration and metabolic response in relation to patient-reported outcomes
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Intervertebral disc degeneration (IVDD) is a significant cause of pain and disability worldwide. IVDD symptom development and surgical outcomes vary greatly between individuals. Clinical evaluation uses patient-reported outcome measures (PROMs) such as the Oswestry Disability Index (ODI), Neck Disability Index (NDI), and Patient-Reported Outcomes Measurement Information System (PROMIS) Global Physical Health (PGPH) to guide treatment decisions and evaluate surgical effectiveness. However, these outcome measurements are a subjective tool and do not reflect the underlying biological factors influencing IVDD symptoms and recovery. To address this gap, protein biomarkers may provide biological insights into the development of symptomatic IVDD and patient outcomes following surgical intervention. First, we systematically reviewed the literature to assess the ability of protein biomarkers to differentiate symptomatic from asymptomatic IVDD. Across the 20 studies reviewed, 58 biomarkers were assessed in serum, disc tissue, or lavage fluid. The most frequently studied protein biomarkers included IL-6, TNF-α, IL-1β, IL-8, MMP-1, IL-17, and IFN-γ. IL-6 was associated with symptom severity, while other markers showed variability based on sample type and patient population. Notably, few studies directly assessed biomarker associations with PROMs, highlighting a critical need for translational studies. To address this, we recovered intervertebral disc tissue from 340 surgical patients to evaluate the associations between tissue protein content and PROMs at preoperative, 3-month, 6-month, and 12 months postoperative time points, as well as the changes in PROM scores over time. Twenty-six protein biomarkers related to inflammation, degradation, and bone metabolism were quantified. PROMs were used to stratify patients into functional groups and minimal clinical important difference (MCID) based change groups. Significant differences in biomarker concentrations were observed between PROM groups, particularly for the ODI, which demonstrated the strongest and most consistent associations with biomarker expression. Patients with higher ODI scores and lower PGPH scores exhibited elevated levels of pro-inflammatory (RANTES, MIP-1α, MIP-1β), prodegradative (MMP-9), and bone-regulating proteins (SOST, OC), while those with improved postoperative outcomes had lower concentrations of several of these markers. Conversely, limited associations were found with NDI and PGPH scores, suggesting that these measures may be less reflective of underlying molecular changes in the disc tissue. Among all biomarkers, RANTES and SOST were most consistently associated with disability and recovery, while elevated MMP-9 and PRG4 levels were particularly notable in patients with severe symptoms. These results underscore the potential of tissue biomarkers to inform prognosis and individualize treatment strategies in patients undergoing surgery for intervertebral disc degeneration.
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M.S.